Silver cathode activation

ABSTRACT

The selective electrochemical reduction of halogenated 4-aminopicolinic acids is improved by activating the cathode at a final potential from about +1.0 to about +1.8 volts.

FIELD OF THE INVENTION

This application claims the benefit of U.S. Provisional Application Ser.No. 61/255,187 filed on 27 Oct. 2009. The present invention concerns animproved process of activating the silver cathode for the selectiveelectrochemical reduction of halogenated pyridines and picolinic acids.

BACKGROUND OF THE INVENTION

U.S. Pat. Nos. 4,217,185, 4,242,183 and 6,352,635 B2 and U.S. PatentApplication Publication 2009/0090639 describe the preparation of certainhalopyridine and halopicolinic acid derivatives by the selectiveelectrochemical reduction of the corresponding higher halogenatedpyridine and picolinic acid derivatives. in this process, the silvercathode is activated by an anodization that involves increasing thepotential from an initial value of zero volts to a final value of atleast +0.3 volts and preferably about +0.7 volts. Because ofpassivation, however, the reaction rate typically slows down asconversion proceeds and it is sometimes necessary to reactivate thecathode by re-anodization to finish a batch. It would be desirable tohave an improved method for activating the cathode that is moreresistant to passivation and would allow shorter reaction times.

SUMMARY OF THE INVENTION

It has now been found that, by activating the cathode at a finalpotential from about +1.0 to about +1.8 volts, the reaction rate isfaster, and the cathode does not need to be reactivated as often tofinish a batch. More particularly, the present invention concerns animproved process for the preparation of a 3-halopyridine or3-halopicolinic acid of Formula I

wherein

X represents Cl or Br;

Y represents H, F, Cl, Br or C₁-C₄ alkyl, with the proviso that when Xis Cl, Y is not Br;

R¹ represents Cl or CO₂H; and

R² represents H or NH₂

in which a direct or alternating electric current is passed from ananode to a silver cathode through a solution of a 3,5-dihalopyridine or3,5-dihalopicolinic acid of Formula II

wherein

X, Y, R¹ and R² are as previously defined, and

wherein

both of X are either Cl or Br,

at a cathode potential of about −0.4 to about −1.7 volts relative to anAg/AgCl (3.0 M Cl⁻) reference electrode, the improvement characterizedby activating the cathode at a final potential from about +1.0 to about+1.8 volts, preferably about +1.2 volts.

This improvement is particularly advantageous for the production of4-amino-3,6-diehloropyridine-2-carboxylic acid (aminopyralid) from4-amino-3,5,6-trichloropyridine-2-carboxylic acid (picloram).

DETAILED DESCRIPTION OF THE INVENTION

The present invention concerns an improved process for the selectiveelectrochemical reduction of the 5-halo substituent of a3,5-dihalopyridine or a 3,5-dihalopicolinic acid. As used herein, theterm “halogen” or “halo” refers to Cl or Br. Alkali metal means lithium,sodium, potassium, rubidium and cesium with sodium and potassium beingpreferred.

The reactions involved in the reduction of for example, a4-amino-3,5-dihalopicolinic acid may be depicted as follows:

A) Neutralization:

B) Cathode Reaction:

C) Anode Reaction:

2 (OH⁻)→½ O₂+H₂O+2e⁻

D) Overall Reaction:

The carboxylic acid is recovered by acidifying the reaction mixture andrecovering the product by conventional techniques.

The desired electrolytic reduction is carried out by techniques that aregenerally known in the art. In general, the starting material of FormulaII is dissolved in a solvent to form an electrolyte which is added tothe electrolytic cell while enough current is passed through theelectrolyte until the desired degree of reduction is obtained.

It should be appreciated by those skilled in the art that the reductionpotential of an aryl bromide is about 0.5 volt higher (less negative)than the comparable aryl chloride potential. The bromine will always bereduced off first. Thus, when X is Cl, Y cannot be Br.

The design of the electrolysis cell is flexible. The electrolysis can beconducted batchwise, or in a continuous or semi-continuous fashion. Thecell may be a stirred tank containing the electrodes or a flow cell ofany conventional design. In some cases, it may be desirable to employ aseparator to divide the cell into separate anodic and cathodiccompartments. Examples of useful separator materials are various anionand cation exchange membranes, porous Teflon, asbestos, and glass. Whilethe use of three electrodes in which the potential of the cathode iscontrolled relative to a reference electrode is preferred, theelectrolysis can alternatively be performed using only two electrodes,an anode and a. cathode, and controlling either the cell current, thecell voltage, or both. For convenience, a 3-electrode undivided cell inwhich the electrolyte serves as both the catholyte and the anolyte ispreferred.

The anode can be any chemically inert material including, for example,platinum, graphite, carbon, metal oxides such as silver, oxide onsilver, or alloys such as Hastelloy C, with graphite, carbon andHastelloy C being preferred. The cathode is primarily constructed ofsilver. Electrodes may be in the form of plates, rods, wires, screens,gauze, wool, sheets or pools, with expanded mesh screens beingpreferred. The anode or cathode may also consist of a coating applied toanother material, an example of which is a noble metal oxide such asruthenium oxide coated onto titanium.

The most preferred cathodes are activated silver cathodes prepared asdescribed in U.S. Pat. Nos. 4,217,185 and 4,242,183. Such activatedcathodes can be prepared by depositing a layer of silver microcrystalson a conductive substrate to form a composite electrode or byanodization of a silver electrode itself. For example, to illustrate thelatter, an unactivated silver electrode can be dipped or immersed in anaqueous caustic catholyte solution and anodized, thus converting some ofthe silver at the surface of the electrode to silver oxide androughening the surface at the same time. The polarity of the electrodeis then reversed and the oxide electrolytically converted into particlesof microcrystalline silver adhered to the surface of the electrode. Theimproved activation procedure of the present invention involvesincreasing the potential from an initial value of zero volts to a finalvalue of at least +1.0 volts to about +1.8 volts, most preferably about+1.2 volts. Reduction of he oxide deposit requires negative polarizationof the cathode. The cathode potential is gradually reduced from thevalue of about +1.0 to about +1.8 volts attained during the oxidationstep, to a value of about −0.5 volts or less. It is not necessary to addany silver to the catholyte or aqueous base in this method.

Typically, the cathode is activated in the presence of from about 0.5 toabout 4 wt % of an alkali metal chloride, bromide or sulfate, preferablyNaCl, an excess of alkali metal hydroxide, preferably from about 1.0 toabout 4.0 wt % NaOH, and the additional presence of the startingmaterial to be reduced. Conveniently, the starting material is presentin the same concentration as it is in the reaction feed, i.e., fromabout 1 to about 20 wt %, preferably from about 8 to about 12 wt %.

Water is the most preferred solvent for the electrolysis but, in somecircumstances, it is possible to use an organic solvent either alone oras a co-solvent. The solvent or the co-solvent system should dissolveall or most of the starting material and the electrolyte, or at leastenough to allow the reduction to proceed at a reasonable rate. Inaddition, the solvent or the co-solvent system should be inert to theelectrolysis conditions, i.e., it does not detrimentally alter or reactwith the cathode or the catholyte materials to an intolerable extent,Other than water, preferred solvents/co-solvents are miscible with waterand include lower molecular weight alcohols, ethers such astetrahydrofuran, dioxane and polyglycol ethers, and lower amides such asdimethylformamide or dimethylacetamide.

Alkali metal hydroxides are needed as the supporting electrolyte andNaOH and KOH arc the most preferred supporting electrolytes, While NaClis the preferred salt, other salts can he used, including alkalichlorides, bromides, and sulfates.

In the reaction, one equivalent of base is required to neutralize thestarting material in the case of a 3,5-dihalopicolinic acid, and anadditional equivalent is required to generate hydroxyl ions that areconsumed in the electrolysis. The reaction is typically conducted withan excess of base, preferably with a 1 to 4 weight percent excess ofbase throughout the reaction.

The concentration of 3,5-dihalopyridine or a 3,5-dihalopicolinic acid inthe catholyte or feed can be from about 1 to about 20 percent by weight,preferably from about 8 to about 12 percent by weight. Lowerconcentrations 1 duce productivity while higher concentrations usuallyresult in lower yields, lower product purity and lower electricalefficiencies.

Suitable temperatures for the electrolysis generally range from about 5to about 90° C. The preferred temperature range is from about 20 toabout 60° C. From about 30 to about 50° C. is most preferred.

One skilled in the art will appreciate that the apparent cathodepotential at which the halogen will be selectively reduced is dependenton a variety of factors including, for example, the structure of theparticular substrate, the cell configuration, and the distanceseparating the electrodes. In general, the cathode potential, relativeto a standard Ag/AgCl (3.0 M Cl⁻) electrode, should be within the rangeof about −0.4 to about −1.1 volts for Br and within the range of about−0.8 to about −1.7 volts for Cl. For Br, the cathode potential ispreferably from about −0.6 to about −0.9 volts. For Cl, the cathodepotential is preferably from about −1.0 to about −1.4 volts. The currentdensity in amperes per square centimeter (amp/cm²) should be at least0.005, preferably about 0.05 amp/cm² or greater.

While the evolution of molecular oxygen is preferred, many other anodicreactions can be employed. Examples include the evolution of molecularchlorine or bromine, oxidation of a sacrificial species such as formateor oxalate to give carbon dioxide, or the oxidation of an organicsubstrate to form a valuable co-product.

in the presently preferred mode of operation for a 3,5-dihalopicolinicacid, the starting material is dissolved in aqueous caustic brine toform a basic aqueous solution (e.g., ˜10 wt % halogenated4-aminopicolinic acid, ˜2.5 wt % excess NaOH and ˜1 wt % NaCl) which iscontinuously recirculated through an undivided electrochemical cellhaving an expanded silver mesh cathode activated by anodization at +1.2volts in the presence of the feed solution. While keeping the reactionmixture alkaline, electrolysis at a cathode potential of from about −0.6to about −1.5 volts relative to an Ag/AgCl (3.0 M Cl⁻) referenceelectrode is continued until the desired degree of reduction hasoccurred. The desired product is recovered by conventional techniques.For example, the acid can be precipitated from the reaction mixture byacidification followed by either filtration or extraction with a waterimmiscible organic solvent.

The following examples are illustrative of the present invention.

EXAMPLES Preparation of 4-amino-3,5,6-trichloropyridine-2-carboxylicAcid (picloram) Feed Solution

To a 4-liter (L) flask was added 2420 grams (g) of hot water, 250 g of50 percent by weight NaOH, 30 g of NaCl, and 300 g of picloram (95percent). The solution was stirred for 30 minutes (min), filteredthrough a 1 micron polypropylene film., and transferred to a 5-L feedcirculation tank. This solution weighed 3000 g and contained 9.5 weightpercent 4-amino-3,5,6-trichloropyridine-2-carboxylic acid, 2.0 to 2.5percent of excess NAM, and 1.0 percent of Nan. This feed solution wasused in both the comparative example and the improved example for thisdisclosure.

Example A Preparation of 4-amino-36-dichloropyridine-2-carboxylic AcidWith Anodization at 0.7 Volts (Comparative)

To an undivided electrochemical cell was added 500 g of the picloramfeed solution. This feed solution was circulated at a rate of 4 Litersper minute (L/min) and a temperature of 43-45° C. through one undividedelectrochemical cell. The size of the silver mesh electrode was 1.8cm×15.4 cm. After normal anodization at +0.7 volts (V), the polarity ofthe cell was reversed and the electrolysis was started. The cathodeworking potential was controlled at −1.35 V relative to an Ag/AgCl (3.0M Cl⁻) reference electrode. While recirculating the feed, a total of 10mL of 50 percent by weight NaOH were added over the first 5 hours tomaintain the NaOH concentration at 1.5-3.0 percent excess. The currentstarted at 5.0 amps and slowly decreased to 0.6 amp at 24 hours.

No more anodization was needed after the electrolysis was started. At 8hours, the cell effluent has 68% aminopyralid and 26% picloram (both inHPLC area %). At 24 hours, the cell effluent had 88% aminopyralid and3.2% picloram.

Example 1 Preparation of 4-amino-3,6-dichloropyridine-2-carboxylic AcidWith Anodization at ±1.2 Volts

To the same undivided electrochemical cell in Example A was added 500 gof the picloram feed solution. This feed solution was circulated at arate of 4 L/min and a temperature of 43-45° C. through one undividedelectrochemical cell. After normal. anodization at +1.2 volts (V), thepolarity of the cell was reversed and the electrolysis was started, Thecathode working potential was controlled at −1.35 V relative to anAg/AgCl (3.0 M Cl⁻) reference electrode. While recirculating the feed, atotal of 10 mL of 50 percent by weight NaOH were added over the first 5hours to maintain the NaOH concentration at 1.5-3.0 percent excess. Thecurrent started at 6.5 amps and slowly decreased to 0.7 V at 2.4 hours.

No more anodization was needed after the electrolysis was started. At 8hours, the cell effluent had 76% aminopyralid and 17% picloram (both inHPLC area %), At 24 hours, the cell effluent had 88% aminopyralid and1.2% picloram.

1. A method for preparing a compound, the method comprising the stepsof: activating a silver cathode by anodizing the cathode at a finalpotential in the range of +1.02 to +1.8 volts; passing a direct oralternating electric current from an anode to the activated silvercathode through a solution of a 3,5-dihalopyridine or3,5-dihalopicolinic acid of Formula (II)

wherein: X represents Cl or Br; Y represents H, F, Cl, Br or C₁-C₄alkyl, with the proviso that when X is Cl, Y is not Br; R¹ represents Clor CO₂H; and R² represents H or NH₂; and forming a 3-halopyridine or3-halopicolinic acid of Formula I

wherein: X represents Cl or Br; Y represents H, F, Cl, Br or C₁-C₄alkyl, with the proviso that when X is Cl, Y is not Br; R¹ represents Clor CO₂H; and R² represents H or NH₂.
 2. The method of claim 1, furtherincluding the step of reversing the polarization of the activatedcathode.
 3. The method of claim 1, in which the 3 halopicolinic acid ofFormula I is aminopyralid and the 3,5-dihalopicolincic acid of FormulaII is picloram.
 4. The method of claim 2, in which the 3 halopicolinicacid of Formula I is aminopyralid and the 3,5-dihalopicolincic acid ofFormula II is picloram.